EP1246784A1 - Reaction de composes carbonyle avec des reactifs organo-metalliques - Google Patents
Reaction de composes carbonyle avec des reactifs organo-metalliquesInfo
- Publication number
- EP1246784A1 EP1246784A1 EP01900150A EP01900150A EP1246784A1 EP 1246784 A1 EP1246784 A1 EP 1246784A1 EP 01900150 A EP01900150 A EP 01900150A EP 01900150 A EP01900150 A EP 01900150A EP 1246784 A1 EP1246784 A1 EP 1246784A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- reaction
- solvent
- temperature
- mini
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/20—Jet mixers, i.e. mixers using high-speed fluid streams
- B01F25/23—Mixing by intersecting jets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/40—Static mixers
- B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
- B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
- B01F25/432—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction with means for dividing the material flow into separate sub-flows and for repositioning and recombining these sub-flows; Cross-mixing, e.g. conducting the outer layer of the material nearer to the axis of the tube or vice-versa
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/24—Stationary reactors without moving elements inside
- B01J19/2415—Tubular reactors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B49/00—Grignard reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00002—Chemical plants
- B01J2219/00004—Scale aspects
- B01J2219/00011—Laboratory-scale plants
- B01J2219/00013—Miniplants
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00051—Controlling the temperature
- B01J2219/00054—Controlling or regulating the heat exchange system
- B01J2219/00056—Controlling or regulating the heat exchange system involving measured parameters
- B01J2219/00058—Temperature measurement
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00051—Controlling the temperature
- B01J2219/00054—Controlling or regulating the heat exchange system
- B01J2219/00056—Controlling or regulating the heat exchange system involving measured parameters
- B01J2219/00065—Pressure measurement
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00051—Controlling the temperature
- B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
- B01J2219/00087—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor
- B01J2219/00094—Jackets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00177—Controlling or regulating processes controlling the pH
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00889—Mixing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00984—Residence time
Definitions
- the invention relates to a new process for carrying out reactions of carbonyl compounds with organometallic reagents, in particular with Grignard reagents.
- the selectivity or quality of a chemical reaction is strongly influenced, among other things, by the precise control of temperature and residence time.
- An example of this is a reaction which is described in patent application DE 44 11 101 A1 (improved process for the preparation of a D - (+) - biotin intermediate "). This is the following reaction:
- the task is solved by a method for carrying out
- Reactions of carbonyl compounds with organometallic reagents which is characterized in that a) the organometallic reagent is placed in a solvent and tem perated, b) the carbonyl compound is separately placed in a suitable solvent and tempered, c) the solutions from a) and b) are pumped into a temperature-controlled mini / micromixer for reaction, optionally through a downstream dwell path in the form of a very thin line, which can also be temperature-controlled, with a defined one
- Residence time is set, d) the emerging reaction mixture is then optionally reacted in a downstream reaction and e) the product mixture obtained is worked up.
- a plate-shaped micromixer is used as the temperature-controlled mini / microreactor in the process according to the invention, in which the starting materials are optionally brought together in a 180 ° T piece and an intensive one
- Grignard reagents and organolithium compounds can be used as organometallic reagents in the process. Accordingly, compounds from group 1, 4-dichloromagnesium butane, 3,4,5-trifluoro-1-bromomagnesium benzene and n-butyllithium can be used.
- a compound selected from the group of aliphatic, cycloaliphatic and heterocyclic ketones can be used as the carbonyl compound.
- the process according to the invention for converting organometallic compounds with carbonyl compounds selected from the group 4- (pentylcyclohexyl-1) -cyclohexan-4-one (4) and (+) - cis-1,3-dibenzyl-hexahydro-1 H is particularly advantageous thieno [3,4-d] imidazole-2,4-dione.
- An aprotic nucleophilic solvent can be used as the solvent for the organometallic compound but also for the carbonyl compound.
- Solvents selected from the group consisting of tetrahydrofuran, diethyl ether, dioxane and dibutyl ether are suitable.
- the process according to the invention can be carried out at a constant temperature between -40 to +120 ° C., preferably up to 60 ° C.
- reaction mixture emerging from the mini / micromixer is conveyed with a downstream pump into a storage tank or stirred reactor.
- a reaction with carbon dioxide or hydrolysis can take place as a subsequent reaction.
- the reaction can be carried out with intensive mixing with a defined residence time. At the same time, it is ensured under these conditions that the reaction mixture is kept constant at almost a specified temperature during the reaction in the reactor under almost ideal conditions, depending on the starting materials used, between -40 and optionally +120 ° C.
- the solutions of the educts Grignard reagent and thiolactone are mixed intensively in a continuously operated mini / microreactor at a defined temperature in the production of the above-mentioned intermediate for the production of biotin.
- the resulting preliminary product after it has been passed through a subsequent very thin, temperature-controlled residence time after it has emerged from the microreactor, is carboxylated with carbon dioxide in a subsequent suitable reactor.
- the process parameters pressure, temperature and mass flows are measured and controlled at various points
- the process described is generally suitable for the implementation of organometallic reagents with carbonyl compounds, since the process parameters concentration ratio, pressure, temperature and flow or residence time can be set exactly. With the possibility of precise reaction control and the use of small reactor volumes, a high level of safety is achieved in this way.
- the procedure is as follows: the thiolactone (1) is dissolved in tetrahydrofuran with the Grignard compound (2) optionally in a micro- or mini-reactor with a subsequent residence time section (residence time: ⁇ ⁇ 10 s) implemented continuously.
- the preliminary product is fed directly into an agitator apparatus filled with gaseous carbon dioxide.
- the further processing of the raw product corresponds to the batch Method as also described in DE 44 11 101 A1.
- the analytical data (NMR, DC) agree with those of the batch reaction.
- FIG. 4 shows a basic structure of a plant for the implementation of carbonyl compounds with organometallic reagents.
- the educts (1) and (2) are initially introduced into the two storage tanks or stirred tanks (I) and (II). Pressure and temperature sensors as well as flow measurements are installed at various points in order to be able to optimally control the process. Furthermore, it makes sense if pre-tempering sections are integrated in the feed lines upstream of the reactor (III). It is also possible to connect several reactors in series, which means that multi-stage reactions can also be carried out.
- pumps are interposed in the model plant in FIG. 4. After exiting the static mini / microreactor, the reaction mixture is passed into a downstream storage tank or stirred tanks (IV) in which a downstream reaction, such as. B. the implementation can be done with C0 2 .
- a suitable system can also be constructed in such a way that a pump is connected downstream of the reactor in order to avoid an undesirable build-up of pressure.
- a standard agitator apparatus which also served as a storage vessel, was used to display the Grignard connection.
- a template with a stirrer was used as the storage vessel for the thiolactone solution.
- a template with a stirrer was used as the storage vessel for the thiolactone solution.
- a standard agitator apparatus served as a collecting vessel for the Grignard addition product and its further implementation with C0 2 .
- a steel container was used as a storage container for solvents (solvent ⁇ LM).
- the educt solutions were conveyed with suitable pumps through a filtration unit under control of the pressure and through check valves into the mini / microreactors.
- the thiolactone solution was tempered using a heat exchanger.
- the temperature-controlled mini reactor consisted of a mixing and reaction unit. The exit of the reaction unit led to the above. Stirred apparatus. A three-way valve located behind the reactor made it possible to take samples.
- a suitable data acquisition and control system was connected to control and record the reaction parameters.
- the 130 I agitator apparatus was evacuated several times and aerated with nitrogen. 2.87 kg (116.9 mol) of magnesium chips (99%) were introduced and inerted the apparatus again with nitrogen. Then 4.2 kg of THF was overlaid, the jacket temperature was set to 70 ° C., and 4.0 kg of a solution of 7.5 kg (59.1 mol) of 1,4-dichlorobutane (> 99%) in 38.8 kg of THF were added. The reaction was started by adding about 50 ml of 1,4- (dichloromagnesium) butane. The jacket temperature was then reset to 60 ° C.
- FIG. 5 A flow diagram of the system used is shown in Fig. 5.
- the system is made up of the following components:
- Pressure transmitter P41 [steel membrane, M20 x 1.5, 0-10 bar absolute pressure, from PMH (Prozess- und Maschinen-Automation GmbH (Philips, D)]
- Massflo ® type Mass 3000/2100 Ex (transmitter and sensor), Danfoss Antriebs- und Regeltechnik GmbH
- the Grignard flow was set to 30 kg / h (3 kg were pumped into the 800 I RWA without reaction with thiolactone) and the thiolactone flow was adjusted using a factor (density difference). This operating setting (30 kg / h) was maintained until the Grignard solution was completely used up.
- the C0 2 flow had to be set to approx. 25 l / h.
- the temperature at the outlet of the mixer was approximately 2 hours 31-33 ° C and the rest of the time approximately 28-29 ° C.
- a pressure increase of approximately 1 bar was observed in the entire system.
- the temperature of the Grignard solution was set at 30 ° C.
- the control behavior of the Grignard pump increased by approx. 10 units.
- the maximum pressure in the system was approximately 4.5 bar at the end of the test.
- cyclohexyl-cyclohexan-3-one can be reacted with 3,4,5-trifluoro-1-bromomagnesium benzene at temperatures between 0 and 60 ° C.
- the dwell time can be reduced from several hours to less than 10 s.
- the yield and thus the product quality can be optimized by increasing the pressure and temperature, although it should be noted that the Grignard
- T-piece mixer 2 Static mixer as in Fig. 2 with an inner diameter of the lines in
- T-piece (III) of 4 mm in which, however, after the starting materials (1) and (2) have been brought together, the reaction mixture is passed through a static mixer with pigtail-shaped lines (5) with an inner diameter of approximately 4 mm.
- Components of the system are:
- Pall cartridge filter Pall cartridge filter; Stainless steel barrel, pressure resistant; 6 mm and 100 mm steel tubes; Swadgelok connectors, taps and hoses.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10001317A DE10001317A1 (de) | 2000-01-14 | 2000-01-14 | Reaktion von Carbonylverbindungen mit metallorganischen Reagenzien |
DE10001317 | 2000-01-14 | ||
PCT/EP2001/000248 WO2001051434A1 (fr) | 2000-01-14 | 2001-01-10 | Reaction de composes carbonyle avec des reactifs organo-metalliques |
Publications (3)
Publication Number | Publication Date |
---|---|
EP1246784A1 true EP1246784A1 (fr) | 2002-10-09 |
EP1246784B1 EP1246784B1 (fr) | 2005-10-19 |
EP1246784B9 EP1246784B9 (fr) | 2006-01-18 |
Family
ID=7627500
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01900150A Revoked EP1246784B9 (fr) | 2000-01-14 | 2001-01-10 | Reaction de composes carbonyle avec des reactifs organo-metalliques |
Country Status (7)
Country | Link |
---|---|
US (1) | US7098344B2 (fr) |
EP (1) | EP1246784B9 (fr) |
JP (1) | JP2003523960A (fr) |
AT (1) | ATE307101T1 (fr) |
AU (1) | AU2001223737A1 (fr) |
DE (2) | DE10001317A1 (fr) |
WO (1) | WO2001051434A1 (fr) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10108471C1 (de) | 2001-02-22 | 2002-11-21 | Boehringer Ingelheim Pharma | Kontinuierliches Verfahren zur Herstellung von 5,6-Dihydro-4-hydroxy-2-pyronen |
US7141681B2 (en) | 2001-02-22 | 2006-11-28 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Continuous process for preparing dihydropyrones |
DE10143189A1 (de) * | 2001-09-04 | 2003-03-20 | Clariant Gmbh | Verfahren und Vorrichtung zur prozeßbegleitenden Reinigung von Mikro-und Minireaktoren |
JP4639042B2 (ja) * | 2003-09-29 | 2011-02-23 | 富士フイルムファインケミカルズ株式会社 | ハロゲン−リチウム交換反応を用いる有機化合物の製造法 |
EP1889849A1 (fr) * | 2006-07-18 | 2008-02-20 | Lonza Ag | Réactions du type grignard effectuée a des micro-reacteurs |
US20100022771A1 (en) * | 2006-09-19 | 2010-01-28 | Noriyuki Yoneda | Reaction apparatus, and reaction method |
CN108002981A (zh) * | 2017-12-11 | 2018-05-08 | 万华化学集团股份有限公司 | 一种连续化生产乙烯基-β-紫罗兰醇的方法 |
CN108164389B (zh) * | 2018-01-29 | 2020-07-10 | 浙江大学 | 一种高选择性2-甲基烯丙基氯的合成方法及合成反应器 |
WO2020164217A1 (fr) * | 2019-02-15 | 2020-08-20 | Fujian Yongjing Technology Co., Ltd | Nouveau procédé de fabrication de composés fluoroaryles et de dérivés |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE759513A (fr) * | 1969-11-29 | 1971-05-27 | Hoffmann La Roche | Thiolactone |
US5358670A (en) * | 1993-07-02 | 1994-10-25 | Ferro Corporation | Process for preparing grignard reagents in diethylene glycol dibutyl ether |
JP3561938B2 (ja) * | 1993-12-27 | 2004-09-08 | 住友化学工業株式会社 | チオファン誘導体の製造法 |
DE4411101C2 (de) * | 1994-03-30 | 1996-02-01 | Merck Patent Gmbh | Verfahren zur Herstellung eines D-(+)-Biotin-Zwischenproduktes |
CA2193774C (fr) * | 1995-12-26 | 2005-02-01 | Norihiko Hirata | Procede de production de l'acide 1-hydroxythienoimidazole-carboxylique et de l'acide thienoimidazole-carboxylique |
DE19746583A1 (de) * | 1997-10-22 | 1999-04-29 | Merck Patent Gmbh | Mikromischer |
GB9723260D0 (en) | 1997-11-05 | 1998-01-07 | British Nuclear Fuels Plc | A method of performing a chemical reaction |
DE19816886C2 (de) * | 1998-04-17 | 2001-06-07 | Axiva Gmbh | Verfahren und Vorrichtung zur kontinuierlichen Herstellung von Polymerisaten |
DE19858856A1 (de) * | 1998-12-19 | 2000-06-21 | Merck Patent Gmbh | Verfahren zur Herstellung von Arylmetallverbindungen und deren Umsetzung mit Elektrophilen |
-
2000
- 2000-01-14 DE DE10001317A patent/DE10001317A1/de not_active Withdrawn
-
2001
- 2001-01-10 DE DE50107745T patent/DE50107745D1/de not_active Revoked
- 2001-01-10 JP JP2001551818A patent/JP2003523960A/ja active Pending
- 2001-01-10 WO PCT/EP2001/000248 patent/WO2001051434A1/fr active IP Right Grant
- 2001-01-10 AU AU2001223737A patent/AU2001223737A1/en not_active Abandoned
- 2001-01-10 AT AT01900150T patent/ATE307101T1/de not_active IP Right Cessation
- 2001-01-10 US US10/169,310 patent/US7098344B2/en not_active Expired - Fee Related
- 2001-01-10 EP EP01900150A patent/EP1246784B9/fr not_active Revoked
Non-Patent Citations (1)
Title |
---|
See references of WO0151434A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP1246784B9 (fr) | 2006-01-18 |
US20030004357A1 (en) | 2003-01-02 |
EP1246784B1 (fr) | 2005-10-19 |
AU2001223737A1 (en) | 2001-07-24 |
DE50107745D1 (de) | 2006-03-02 |
DE10001317A1 (de) | 2001-07-19 |
ATE307101T1 (de) | 2005-11-15 |
WO2001051434A1 (fr) | 2001-07-19 |
JP2003523960A (ja) | 2003-08-12 |
US7098344B2 (en) | 2006-08-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1965901A2 (fr) | Procede pour creer des composes couples aryle-aryle | |
EP1246784B9 (fr) | Reaction de composes carbonyle avec des reactifs organo-metalliques | |
EP1272482A1 (fr) | Procede servant a realiser une oxydation de baeyer-villiger de composes carbonyles organiques | |
DE69823824T2 (de) | Melamin-synthese-anlage und melamin synthese | |
EP3374353B1 (fr) | Procédé pour la réactivation d'un catalyseur d'oxydation homogène | |
EP1379464A2 (fr) | Procede pour produire des solutions organiques de peroxyde d'hydrogene | |
EP3539943A1 (fr) | Procédé de préparation de la n-alkyl-nitratoethylnitramine | |
EP1892231A1 (fr) | Méthode de déoxofluoration de cétones à l'échelle industrielle | |
DE19738085C1 (de) | Verfahren zur Herstellung von Feststoffen durch Fällung | |
WO2001009064A1 (fr) | Acylation de friedel-crafts dans un micromelangeur statique | |
EP0244687A2 (fr) | Procédé de préparation de pigments azoiques | |
EP1268406A1 (fr) | Procede d'oximation de composes carbonyle organiques et/ou de composes acides ch | |
WO2009071409A1 (fr) | Procédé pour dissoudre des concentrés d'oxyde de molybdène | |
WO2001092187A1 (fr) | Procede de formylation de composes organiques | |
WO2001074822A1 (fr) | Procede de cycloaddition 1,3-dipolaire de composes organiques dans un microreacteur | |
WO2001092225A1 (fr) | Procede de preparation d'indols | |
DE2723247C2 (de) | Verfahren zur kontinuierlichen Herstellung von 3-Nitro-4-acetylaminotoluol | |
EP1419134B1 (fr) | Procede de production de nitrites d'alkyle et de dinitrites d'alkyle | |
WO2003011811A1 (fr) | Procede de fabrication continue de 2-bromo-2-nitro-1,3-propane diol | |
DE1442659B2 (de) | Verfahren und vorrichtung zur kontinuierlichen faellung von gelartigen produkten, insbesondere pigmenten, aus waessrigen loesungen entsprechender metall salze | |
DE60200217T2 (de) | Verfahren zur herstellung von 2,3-dichlor-1-propanol und epichlorhydrin | |
DE2619580C2 (de) | Verfahren zur kontinuierlichen Herstellung a-cyanäthylierter, aliphatischer Aldehyde | |
CH425741A (de) | Kontinuierliches Verfahren zur Herstellung von Chlorcyan | |
DE2848002A1 (de) | Verfahren zur herstellung von hydrazinsulfat | |
EP1200401A1 (fr) | Procede pour la production d'acylguanidines protegees par aldolisation selon mukaiyama |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20020625 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
|
AX | Request for extension of the european patent |
Free format text: AL;LT;LV;MK;RO;SI |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: STOLDT, JOERAN Inventor name: KRUMMRADT, HOLGER Inventor name: MELICHAR, WOLFGANG Inventor name: ZEHNER, STEFAN Inventor name: KOOP, ULRICH Inventor name: SCHWARZ, MICHAEL Inventor name: ECKSTEIN, JUERGEN |
|
17Q | First examination report despatched |
Effective date: 20040308 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20051019 Ref country code: NL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20051019 Ref country code: IE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20051019 |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D Free format text: NOT ENGLISH |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: ECKSTEIN, JUERGEN Inventor name: MELICHAR, WOLFGANG Inventor name: ZEHNER, STEFAN Inventor name: KRUMMRADT, HOLGER Inventor name: SCHWARZ, MICHAEL Inventor name: KOOP, ULRICH Inventor name: STOLDT, JOERAN |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D Free format text: LANGUAGE OF EP DOCUMENT: GERMAN |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20060110 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20060119 Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20060119 Ref country code: SE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20060119 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20060130 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20060131 Ref country code: MC Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20060131 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20060131 |
|
GBT | Gb: translation of ep patent filed (gb section 77(6)(a)/1977) |
Effective date: 20060125 |
|
REF | Corresponds to: |
Ref document number: 50107745 Country of ref document: DE Date of ref document: 20060302 Kind code of ref document: P |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: PT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20060320 |
|
NLV1 | Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents act | ||
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FD4D |
|
ET | Fr: translation filed | ||
PLBI | Opposition filed |
Free format text: ORIGINAL CODE: 0009260 |
|
26 | Opposition filed |
Opponent name: BAYER TECHNOLOGY SERVICES GMBH Effective date: 20060719 |
|
PLAX | Notice of opposition and request to file observation + time limit sent |
Free format text: ORIGINAL CODE: EPIDOSNOBS2 |
|
PLAF | Information modified related to communication of a notice of opposition and request to file observations + time limit |
Free format text: ORIGINAL CODE: EPIDOSCOBS2 |
|
PLAF | Information modified related to communication of a notice of opposition and request to file observations + time limit |
Free format text: ORIGINAL CODE: EPIDOSCOBS2 |
|
BERE | Be: lapsed |
Owner name: MERCK PATENT G.M.B.H. Effective date: 20060131 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: TR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20051019 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20051019 |
|
RDAF | Communication despatched that patent is revoked |
Free format text: ORIGINAL CODE: EPIDOSNREV1 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20090108 Year of fee payment: 9 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20090114 Year of fee payment: 9 Ref country code: GB Payment date: 20090107 Year of fee payment: 9 |
|
RDAG | Patent revoked |
Free format text: ORIGINAL CODE: 0009271 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: PATENT REVOKED |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
27W | Patent revoked |
Effective date: 20090404 |
|
GBPR | Gb: patent revoked under art. 102 of the ep convention designating the uk as contracting state |
Effective date: 20090404 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20090130 Year of fee payment: 9 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF THE APPLICANT RENOUNCES Effective date: 20051019 Ref country code: CH Free format text: LAPSE BECAUSE OF THE APPLICANT RENOUNCES Effective date: 20051019 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20090113 Year of fee payment: 9 |
|
PLAB | Opposition data, opponent's data or that of the opponent's representative modified |
Free format text: ORIGINAL CODE: 0009299OPPO |